Supporting Information

Size: px
Start display at page:

Download "Supporting Information"

Transcription

1 Supporting Information ACA: A Family of Fluorescent Probes that Bind and Stain Amyloid Plaques in Human Tissue Willy M. Chang, a Marianna Dakanali, a Christina C. Capule, a Christina J. Sigurdson, b Jerry Yang,* a Emmanuel A. Theodorakis *a a Department of Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive MC: 0358, La Jolla, CA , USA. b Department of Pathology, University of California, San Diego, 9500 Gilman Drive MC: 0612, La Jolla, , USA * address: jerryyang@ucsd.edu * address: etheodor@ucsd.edu Supporting Information pages Experimental procedures 2-9 Fluorescent Spectra Kd determination MR spectra

2 General otes All reagents were purchased at highest commercial quality and used without further purification except where noted. Air- and moisture-sensitive liquids and solutions were transferred via syringe or stainless steel cannula. rganic solutions were concentrated by rotary evaporation below 45 C at approximately 20 mmhg. All non-aqueous reactions were carried out under anhydrous conditions. Yields refer to chromatographically and spectroscopically ( 1 H MR, 13 C MR) homogeneous materials, unless otherwise stated. Reactions were monitored by thin-layer chromatography (TLC) carried out on 0.25 mm Dynamic Adsorbents, Inc. silica gel plates (60F-254) and visualized under UV light and/or developed by dipping in solutions of 10% ethanolic phosphomolybdic acid (PMA) and applying heat. Dynamic Adsorbents, Inc. silica gel (60, particle size mm) was used for flash chromatography. MR spectra were recorded on the Varian Mercury 400, 300 and/or Unity 500 MHz instruments and calibrated using the residual non-deuterated solvent as an internal reference. The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, b = broad. High resolution mass spectra (HRMS) were recorded on a VG 7070 HS mass spectrometer under electron spray ionization (ESI) or electron impact (EI) conditions. 6-bromo-2-naphtaldehyde (8) Br 8 H To a solution of DIBAL-H (1.0 M in heptane, 34 ml, 34 mmol) at 0 C under argon, a solution of 7 (3.0 gr, 11 mmol) in anhydrous THF was added dropwise. The reaction mixture was allowed to warm up to room temperature and left stirring overnight. Upon completion, MeH was added, followed by a saturated sodium potassium tartrate solution and ethylacetate. After the two phases were separated, the organic phase was washed with saturated solution of ammonium chloride and brine, dried over MgS 4 and concentrated under reduced pressure to yield 6-bromo-2-(hydroxymethyl)naphthalene. R f = 0.33 (EtAc:Hexanes 3:7); 1 H MR (400 MHz, CDCl 3 ): δ 7.99 (bs, 1H), 7.77 (bs, 1H), 7.74 (d, J= 8.5 Hz, 1H), 7.69 (d, J= 8.7 Hz, 1H), 7.55 (dd, J= 2

3 1.7, 8.7 Hz, 1H), 7.49 (dd, J= 1.7, 8.5 Hz, 1H), 4.84 (bs, 2H); 13 C MR (100 MHz, CDCl 3 ) δ 138.8, 133.9, 131.7, 129.7, 129.5, 129.5, 127.4, 126.1, 125.2, 119.8, To a suspension of pyridinium chlorochromate (2.4 gr, 11 mmol) in anhydrous CH 2 Cl 2 (60 ml) was added a solution of the above alcohol in anh. CH 2 Cl 2, and the reaction was heated under reflux for 5 hours. Upon completion, it was cooled to room temperature and poured into diethyl ether. The solution was then filtered through a pad of silica and concentrated under reduced pressure to yield 8 (2.4 gr, 95%). 8: white solid; R f = 0.67 (EtAc:Hexanes 3:7); 1 H MR (400 MHz, CDCl 3 ) δ (s, 1H), 8.31 (bs, 1H), 8.08 (bs, 1H), 7.98 (dd, J= 1.5, 8.5 Hz, 1H), 7.86 (m, 2H), 7.67 (dd, J= 1.5, 8.5 Hz, 1H); 13 C MR (100 MHz, CDCl 3 ) δ 191.8, 137.3, 134.3, 134.1, 131.0, 131.0, 130.6, 130.2, 128.2, 124.0, General procedure for the synthesis of 6-amino-substituted naphtaldehydes (9-12) In dry and degassed toluene (0.8 ml), were added Pd(Ac) 2 (0.022 mmol) and P(tBu) 3 (0.078 mmol) After stirring for 20 min, 8 (0.207 mmol), the appropriate amine (0.249 mmol) and Cs 2 C 3 (0.280 mmol) were added and the reaction left stirring for three days under reflux. After three days, the reaction was cooled at room temperature, diluted with CH 2 Cl 2, filtered, concentrated under reduced pressure and purified via silica gel flash chromatography (hexanes/etac 0-10%). 6-(piperidin-1-yl)naphthalene-2-carbaldehyde (9). 70% yield, yellow solid; R f = 9 H 0.61 (EtAc:Hexanes 3:7); 1 H MR (400 MHz, CDCl 3 ) δ (s, 1H), 8.15 (s, 1H), 7.83 (m, 2H), 7.68 (d, J= 8.6 Hz, 1H) 7.32 (dd, J= 2.4, 9.1 Hz, 1H), 7.08 (d, J= 2.4 Hz, 1H), 3.38 (m, 4H), (m, 6H); 13 C MR (100 MHz, CDCl 3 ) δ 191.9, 151.9, 138.5, 134.4, 131.3, 130.4, 127.2, 126.3, 123.4, 119.5, 108.8, 49.6, 25.5, 24.3; HRMS Calc for C 16 H 18 (M+H) found

4 6-morpholinonaphthalene-2-carbaldehyde (10). 79% yield, yellow solid; R f = 10 H 0.56 (EtAc:Hexanes 3:7); 1 H MR (400 MHz, CDCl 3 ) δ (s, 1H), 8.20 (s, 1H), 7.88 (m, 2H), 7.73 (d, J= 8.4 Hz, 1H), 7.32 (m, 1H), 7.11 (d, J= 1.2 Hz, 1H), 3.92 (m, 4H), 3.36 (m, 4H); 13 C MR (100 MHz, CDCl 3 ) δ 191.9, 151.3, 138.1, 134.2, 131.8, 130.6, 127.5, 127.0, 123.6, 118.7, 109.0, 66.7, 48.5; HRMS Calc for C 15 H 15 2 a (M+a) found (4-methylpiperazin-1-yl)naphthalene-2-carbaldehyde (11). 77% yield, 11 H yellow solid; R f = 0.36 (EtAc:Hexanes 3:7); 1 H MR (300 MHz, CDCl 3 ) δ (s, 1H), 8.13 (s, 1H), 7.80 (m, 2H), 7.66 (d, J= 8.6 Hz, 1H), 7.28 (dd, J= 2.1, 9.2 Hz, 1H), 7.06 (d, J= 2.1 Hz, 1H), 3.36 (m, 4H), 2.57 (m, 4H), 2.33 (s, 3H); 13 C MR (100 MHz, CDCl 3 ) δ 191.5, 151.0, 138.0, 134.0, 131.3, 130.2, 127.1, 126.4, 123.1, 118.7, 108.7, 54.5, 47.8, 45.7; HRMS Calc for C 16 H 19 2 (M+H) found (2-morpholinoethylamino)naphthalene-2-carbaldehyde (12). 33% H 12 H yield, yellow solid; R f = 0.60 (2% MeH in CH 2 Cl 2 ); 1 H MR (400 MHz, CDCl 3 ) δ (s, 1H), 8.14 (s, 1H), 7.83 (dd, J= 1.6, 8.6 Hz, 1H), 7.76 (d, J= 8.9 Hz, 1H), 7.64 (d, J= 8.6 Hz, 1H), 6.98 (dd, J= 2.3, 8.9 Hz, 1H), 6.79 (d, J= 2.3 Hz, 1H), 4.88 (bs, 1H), 3.75 (m, 4H), 3.31 (dd, J= 5.1, 11.1 Hz, 2H), 2.72 (m, 2H), 2.51 (bs, 4H); 13 C MR (100 MHz, CDCl 3 ) δ 191.9, 148.8, 139.1, 134.6, 130.8, 130.7, 126.6, 126.0, 123.8, 118.7, 103.8, 66.9, 56.7, 53.3, 39.3; HRMS Calc for C 17 H (M+H) found

5 General procedure for the synthesis of 2-cyanoacetates (13) To a solution of 2-cyanoacetic acid (2.72 mmol), the appropriate alcohol (2.27 mmol) in CH 2 Cl 2 (2.5 ml) and DMAP (0.013 mmol) was added dropwise at 0 C. Finally, DCC (2.72 mmol) was added and the reaction mixture was stirred at 0 C for 6 hours. The reaction was diluted with CH 2 Cl 2 and the formed DCU was filtered off. The filtrate was dried over MgS 4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography to yield 2-cyanoacetate 7. C 13a 2 2-(2-(2-methoxyethoxy)ethoxy)ethyl-2-cyanoacetate (13a). 86% yield; colorless liquid; R f = 0.45 (100% ether); 1 H MR (400 MHz, CDCl 3 ) δ 4.29 (m, 2H), 3.67, (m, 2H), 3.59 (m, 6H), 3.50 (m, 2H), 3.49 (s, 2H), 3.32 (s, 3H); 13 C MR (100 MHz, CDCl 3 ) δ 163.0, 113.0, 71.7, 70.4, 70.3, 68.3, 65.5, 58.8, 24.5; HRMS: calcd. for C 10 H 17 5 : (M+H + ) , found C 13b 3 2-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)ethyl-2-cyanoacetate (13b). 68% yield; colorless liquid; R f = 0.40 (100% ether); 1 H MR (400 MHz, CDCl 3 ) δ 4.21 (bs, 2H), 3.61 (bs, 2H), 3.51 (m, 12H), 3.43 (m, 2H), 3.24 (bs, 3H) 13 C MR (100 MHz, CDCl 3 ) δ 163.0, 113.0, 71.4, 70.2, 70.1, 70.1, 70.0, 68.1, 65.3, 58.5, 24.2; HRMS: calcd. for C 12 H 22 6 : (M+H + ) , found C 13c (2,2-dimethyl-1,3-dioxolan-4-yl)methyl 2-cyanoacetate (13c). 71% yield; colorless liquid; R f = 0.83 (100% EtAc); 1 H MR (400 MHz, CDCl 3 ) δ 4.35 (m, 1H), (m, 2H), 4.09 (m, 1H), 3.76 (dd, J= 5.8, 8.6 Hz, 1H), 3.52 (s, 2H), 1.43 (s, 3H), 1.36 (s, 3H); 13 C MR (100 MHz, CDCl 3 ) δ 162.8, 112.7, 110.1, 73.0, 66.8, 65.9, 26.6, 25.2, 24.6; HRMS Calc for C 9 H 13 4 (M+H) found

6 General procedure for the synthesis of fluorescent probes To a round bottom flask containing a solution of aldehyde (0.21 mmol) and the appropriate 2- cyanoacetate (0.23 mmol) in THF (0.8 ml), piperidine (0.02 mmol) was added and the mixture left stirring at 50 C. The reaction was monitored by TLC and was completed within 21 hours. The crude mixture was concentrated under reduced pressure and the product was purified via flash column chromatography (10-30% EtAc in hexanes). C 6 (E)-2-(2-(2-methoxyethoxy)ethoxy)ethyl 2-cyano-3-(2- (piperidin-1-yl)napthalen-6-yl) acrylate (6). 90% yield; red liquid; R f = 0.44 (EtAc:Hexanes 1:1); 1 H MR (400 MHz, CDCl 3 ) δ 8.31 (s, 1H), 8.22 (bs, 1H), 8.10 (d, J= 8.8 Hz, 1H), 7.76 (d, J= 9.2 Hz, 1H), 7.65 (d, J= 8.8 Hz, 1H), 7.30 (dd, J= 2.1, 9.2 Hz, 1H), 7.05 (d, J= 2.1 Hz, 1H), 4.47 (m, 2H), 3.83 (m, 2H), (m, 6H), 3.56 (m, 2H), (m, 4H), 3.37 (s, 3H), 1.74 (m, 6H); 13 C MR (100 MHz, CDCl 3 ) δ 163.3, 155.4, 151.9, 137.7, 134.7, 130.6, 127.2, 126.4, 125.9, 125.6, 119.2, 116.4, 108.3, 71.8, 70.7, 70.5, 70.5, 68.7, 65.3, 58.9, 49.3, 25.4, 24.3; HRMS Calc for C 26 H a (M+a) found C 14 (E)-2-(2-(2-methoxyethoxy)ethoxy)ethyl 2-cyano-3- (2-(4-methylpiperazin-1-yl) napthalen-6-yl)acrylate (14). 85% yield; red liquid; R f = 0.71 (2% MeH in CH 2 Cl 2 ); 1 H MR (400 MHz, CDCl 3 ) δ 8.31 (s, 1H), 8.23 (s, 1H), 8.10 (d, J= 8.6 Hz, 1H), 7.78 (d, J= 9.1 Hz, 1H), 7.67 (d, J= 8.6 Hz, 1H), 7.29 (d, J= 9.1 Hz, 1H), 7.06 (s, 1H), 4.46 (m, 2H), 3.83 (m, 2H), 3.73 (m, 2H), 3.67 (m, 4H), 3.55 (m, 2H) 3.42 (bs, 4H), 3.36 (s, 3H), 2.61 (bs, 4H), 2.37 (s, 3H); 13 C MR (100 MHz, CDCl 3 ) δ 163.2, 155.4, 151.4, 137.5, 134.5, 130.6, 127.4, 126.9, 126.1, 126.1, 119.0, 116.2, 108.7, 99.3, 71.9, 70.8, 70.6, 70.5, 68.8, 65.4, 59.0, 54.8, 48.0, 46.1; HRMS Calc for C 26 H

7 (M+H) found C 15 (E)-2-(2-(2-methoxyethoxy)ethoxy)ethyl 2-cyano-3- (2-morpholinonapthalen-6-yl) acrylate (15). 83% yield; red liquid; R f = 0.76 (2% MeH in CH 2 Cl 2 ); 1 H MR (300 MHz, CDCl 3 ) δ 8.31 (s, 1H), 8.24 (s, 1H), 8.11 (dd, J= 1.9, 8.8 Hz, 1H), 7.80 (d, J= 9.1 Hz, 1H), 7.69 (d, J= 8.8 Hz, 1H), 7.28 (m, 1H), 7.06 (d, J= 1.9 Hz, 1H), 4.47 (m, 2H), 3.90 (m, 4H), 3.83 (m, 2H), 3.70 (m, 6H), 3.55 (m, 2H), 3.35 (m, 7H); 13 C MR (100 MHz, CDCl 3 ) δ 163.0, 155.2, 151.3, 137.2, 134.4, 130.6, 127.4, 127.0, 126.1, 126.0, 118.5, 116.1, 108.5, 99.4, 71.8, 70.7, 70.5, 70.4, 68.6, 66.5, 65.3, 58.9, 48.2; HRMS Calc for C 25 H a (M+a) found H C 16 (E)-2-(2-(2-methoxyethoxy) ethoxy) ethyl3-(2- (2-morpholino ethylamino) naphthalene-6-yl)- 2-cyanoacrylate (16). 87% yield; red liquid; R f = 0.53 (2% MeH in CH 2 Cl 2 ); 1 H MR (500 MHz, CDCl 3 ) δ 8.28 (s, 1H), 8.19 (d, J= 1.6 Hz, 1H), 8.08 (dd, J= 1.9, 8.8 Hz, 1H), 7.69 (d, J= 8.9 Hz, 1H), 7.60 (d, J= 8.8 Hz, 1H), 6.95 (dd, J= 2.3, 8.8 Hz, 1H), 6.74 (d, J= 2.2 Hz, 1H), 4.96 (bs, 1H), 4.46 (m, 2H), 3.83 (m, 2H), (m, 6H), (m, 4H), (m, 2H), 3.36 (s, 3H), 3.31 (s, 2H), 2.70 (m, 2H), 2.51 (s, 4H); 13 C MR (100 MHz, CDCl 3 ) δ 163.4, 155.5, 149.0, 138.3, 135.0, 130.9, 126.6, 126.3, 126.2, 124.9, 118.9, 116.5, 103.6, 98.2, 71.9, 70.8, 70.6, 70.5, 68.8, 66.9, 65.3, 59.0, 56.6, 53.2, 39.2; HRMS Calc for C 27 H (M+H) found

8 C 17 (E)-2-(2-(2-(2-methoxyethoxy) ethoxy)ethoxy)ethyl 2-cyano-3-(2-(piperidin-1- yl)napthalen-6-yl)acrylate (17). 89% yield; red liquid; R f = 0.67 (2% MeH in CH 2 Cl 2 ); 1 H MR (400 MHz, CDCl 3 ) δ 8.20 (s, 1H), 8.10 (s, 1H), 8.01 (d, J= 8.5 Hz, 1H), 7.66 (d, J= 9.0 Hz, 1H), 7.55 (d, J= 9.0 Hz, 1H), 7.20 (d, J= 8.5 Hz, 1H), 6.95 (s, 1H), 4.39 (bs, 2H), 3.75 (bs, 2H), (m, 10H), 3.45 (m, 2H), 3.31 (bs, 4H), 3.28 (s, 3H), (m, 6H); 13 C MR (100 MHz, CDCl 3 ) δ 163.2, 155.3, 151.8, 137.6, 134.6, 130.5, 127.1, 126.3, 125.8, 125.5, 119.1, 116.3, 108.2, 98.4, 71.7, 70.6, 70.4, 70.3, 68.6, 65.3, 58.8, 49.2, 25.3, 24.2; HRMS Calc for C 28 H a (M+a) found C (E)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 2-cyano-3-(2- (piperidin-1-yl)naphthalene-6-yl) acrylate (18). 83% yield; red liquid; R f = 0.25 (EtAc:Hexanes 4:6); 1 H MR (400 MHz, CDCl 3 ) δ 8.29 (s, 1H), 8.19 (s, 1H), 8.09 (dd, J= 1.9, 8.8 Hz, 1H), 7.74 (d, J= 9.3 Hz, 1H), 7.63 (d, J= 8.8 Hz, 1H), 7.28 (dd, J= 2.8, 9.3 Hz, 1H), 7.03 (d, J= 1.9 Hz, 1H), 4.43 (m, 1H), 4.36 (m, 2H), 4.14 (dd, J= 6.0, 8.5 Hz, 1H), 3.90 (dd, J= 6.0, 8.5 Hz, 1H), 3.40 (m, 4H), (m, 6H), 1.48 (s, 3H), 1.39 (s, 3H); 13 C MR (100 MHz, CDCl 3 ) δ 162.9, 155.4, 151.5, 137.6, 134.6, 130.5, 127.0, 126.2, 125.6, 125.3, 119.0, 116.1, 109.6, 108.2, 98.0, 73.1, 65.9, 65.6, 57.1, 49.1, 45.5, 29.4, 26.4, 25.2, 24.0; MS (M+H) C H H (E)-2,3-dihydroxypropyl2-cyano-3-(2-(piperidin-1-yl) naphthalene- 6-yl)acrylate (19). Compound 18 (50 mgr, 0.12 mmol) was dissolved in a mixture of THF/MeH (1:1) and DWEX-H + resin (15 mgr) was added and the heterogeneous mixture was stirred for 20 hours. The resin was removed by 8

9 filtration and triethylamine was added and the solvent was removed under reduced pressure. The residue was purified by flash chromatography to give compound : 38 mgr, 84% yield; red liquid; R f = 0.55 (EtAc:Hexanes 1:4); 1 H MR (400 MHz, CDCl 3 ) δ 8.30 (s, 1H), 8.19 (s, 1H), 8.08 (d, J= 8.8 Hz, 1H), 7.74 (d, J= 9.1 Hz, 1H), 7.63 (d, J= 9.1 Hz, 1H), 7.29 (m, 1H), 7.03 (s, 1H), (m, 2H), 4.09 (m, 1H), 3.81 (dd, J= 5.5, 11.3 Hz, 1H), 3.73 (dd, J= 5.5, 11.3 Hz, 1H), 3.41 (m, 4H), (m, 6H); 13 C MR (100 MHz, CDCl 3 ) δ 163.6, 156.0, 152.0, 137.9, 135.0, 130.7, 127.3, 126.3, 125.9, 125.5, 119.2, 116.6, 108.3, 97.8, 69.9, 67.0, 63.2, 49.3, 25.5, 24.3; HRMS Calc for C 22 H (M+H) found

10 Fluorescence studies with aggregated Aβ peptides Compound 6 Intensity x Wavelength (nm) Before After mixing with Aβ Compound 14 Intensity x Before After mixing with Aβ Wavelength (nm) 10

11 Compound 15 Intensity x Before After mixing with Aβ Wavelength (nm) Compound 16 Intensity x Wavelength (nm) Before After mixing with Aβ 11

12 Compound 17 Intensity x Wavelength (nm) Before After mixing with Aβ Compound Before After mixing with Aβ Intensity x 10 3 Wavelength (nm) 12

13 Determination of binding constant Compound y = Bmax x / (K d + x) R 2 = Bmax = ± K d = ± Intensity (E) Concentration (um) Compound y = Bmax x / (K d + x) R 2 = Bmax = ± K d = ± Intensity (E) Concentration (um) 13

14 Compound y = Bmax x / (K d + x) R 2 = Bmax = ± K d = ± Intensity (E) Concentration (um) Compound y = Bmax x / (K d + x) R 2 = Bmax = ± K d = ± Intensity (E) Concentration (um) 14

15 Compound y = Bmax x / (K d + x) R 2 = Bmax = ± K d = ± Intensity (E) Concentration (um) Compound y = Bmax x / (K d + x) R 2 = Bmax = ± K d = ± Intensity (E) Wavelength (um) 15

16 H Br $"!! $"%* $"&! $"!# $"%' $"%) %"$% )"++ )")) )")# )")& )")! )"() )"#( )"## )"#' )"#& )"#! )"'* )"') '"*' $!"# $!"! +"# +"! *"# *"! )"# )"! ("# ("! #"# #"!,$-.//01 '"# '"! &"# &"! %"# %"! $"# $"!!"#!"! 16

17 "$)1) "$"1( "#*1( "#*1& "#*1& "#(1% "#'1" "#&1# ""*1) '&1# H Br #!! "*! ")! "(! "'! "&! "%! "$! "#! ""! "!! +",-../0 *! )! (! '! &! %! $! #! "!! 17

18 $!"$# *"&$ )"++ )"*+ )"*' )"(* )"(* )"(( )"(( H Br 8 $"!' $"!* $"!! $"!) %"$+ $"!+ $!"# $!"! +"# +"! *"# *"! )"# )"! ("# ("! #"# #"!,$-.//01 '"# '"! &"# &"! %"# %"! $"# $"!!"#!"! 18

19 "*"1) "$(1# "$%1" "$!1' "#)1" "#%1! "#$1' H Br 8 "*! ")! "(! "'! "&! "%! "$! "#! ""! "!! +",-../0 *! )! (! '! &! %! $! #! "!! 19

20 !"!!"# $"! $"# %"! %"# &"! &"# '"! '"# #"! #"# ("! ("# )"! )"# *"! *"# +"! +"# $!"! $!"#,$-.//01 )"%( '"') $"!+ $"!) $"!* %"!* $"!# $"!! $"(' $"(( $"() $"(* $"(* $")% $")& $")' $")( $")) &"&( &"&* &"&+ )"!* )"!+ )"%( )"&$ )"&& )"() )"(+ )"*! )"*% )"*' *"$# $!"!& H 9 20

21 "*"1* "&"1* "$)1& "$%1% "$!1% "#'1$ "#$1% ""*1& "!)1) %*1' #&1& #%1$ H 9 #!! "*! ")! "(! "'! "&! "%! "$! "#! ""! "!! +",-../0 *! )! (! '! &! %! $! #! "!! 21

22 !"!!"# $"! $"# %"! %"# &"! &"# '"! '"# #"! #"# ("! ("# )"! )"# *"! *"# +"! +"# $!"! $!"#,$-.//01 #"!+ #"%* $"&$ $")% $"'+ %"(& $"'% $"!! &"&# &"&( &"&) &"+$ &"+% &"+& )"$$ )"$$ )"%( )"&$ )"&& )")% )")' )"*) )"*+ *"%! $!"!( H 10 22

23 "*"1* "&"1$ "$)1" "$%1# "$!1' "#(1! "#$1' "")1( "!*1! ''1( %)1& H 10 #!! "*! ")! "(! "'! "&! "%! "$! "#! ""! "!! +",-../0 *! )! (! '! &! %! $! #! "!! 23

24 H 11 24

25 H 11 25

26 !"!!"# $"! $"# %"! %"# &"! &"# '"! '"# #"! #"# ("! ("# )"! )"# *"! *"# +"! +"# $!"! $!"#,$-.//01 '"'! %"$# %"$+ '"#$ $"!! $"$( $"%% $"$+ $"&$ $"!) $"!( $"!! %"#$ %")! %")$ %")& &"%+ &"&! &"&% &"&& &")' &")# &")( '"** (")* (")+ ("+) ("+) ("++ )"(& )"(# )")# )")) )"*% *"$' $!"!$ H 12 H 26

27 "*"1* "%)1) "%)1) "$*1" "$%1& "$!1' "#'1! "#$1( "")1( "")1( "!$1* "!$1) ''1* &'1' &$1$ $*1$ H 12 H #!! "*! ")! "(! "'! "&! "%! "$! "#! ""! "!! +",-../0 *! )! (! '! &! %! $! #! "!! 27

28 %"!! %"$( ("!* '"!% %"*$ )"%( '"%+ '"%* '"%) &"() &"#) &"## &"'* &"'( &"&! C 13a 2 $!"# $!"! +"# +"! *"# *"! )"# )"! ("# ("! #"# #"!,$-.//01 '"# '"! &"# &"! %"# %"! $"# $"!!"#!"! 28

29 "'$1! ""$1! ("1' (!1$ (!1$ ')1# '&1& &)1( #%1% C 13a 2 #!! "*! ")! "(! "'! "&! "%! "$! "#! ""! "!! +",-../0 *! )! (! '! &! %! $! #! "!! 29

30 $"!! $"$$ #")! $"$# $"#* )"%( '"%$ &"#$ &"'* &"'& &"'% &"'$ &"%' &"%& C 3 13b $!"# $!"! +"# +"! *"# *"! )"# )"! ("# ("! #"# #"!,$-.//01 '"# '"! &"# &"! %"# %"! $"# $"!!"#!"! 30

31 "'$1! ""$1! ("1% (!1# (!1" (!1" (!1! ')1! '&1# &)1& #%1# C 13b 3 #!! "*! ")! "(! "'! "&! "%! "$! "#! ""! "!! +",-../0 *! )! (! '! &! %! $! #! "!! 31

32 !"!!"# $"! $"# %"! %"# &"! &"# '"! '"# #"! #"# ("! ("# )"! )"# *"! *"# +"! +"# $!"! $!"#,$-.//01 &"!! &"&& $"*+!"**!"+& $"**!"+& $"&( $"'& &"#$ &")' &")( '"!) '"!+ '"$$ '"$+ '"%! '"%$ '"%& '"%# '"%( '"%* '"%+ '"&% '"&& '"&# '"&( '"&) C 13c 32

33 "'#1) ""#1( ""!1" ($1! ''1) '&1* #'1' #&1# #%1' C 13c #!! "*! ")! "(! "'! "&! "%! "$! "#! ""! "!! +",-../0 *! )! (! '! &! %! $! #! "!! 33

34 !"!!"# $"! $"# %"! %"# &"! &"# '"! '"# #"! #"# ("! ("# )"! )"# *"! *"# +"! +"# $!"!,$-.//01 ("(% &"*+ &")% %")& )"'% %"%) %"!% $"$( $"&# $"#$ $"!* $"!) $"!! $"!% $")' &"&) &"&* &"&+ &"'$ &"'% &"## &"#) &"() &")! &")' &"*% '"'( '"') '"'* )"!# )"!# )"%* )"&$ )"(' )"(( )")# )")* *"!+ *"$$ *"%% *"&$ C 6 34

35 ! "! #! $! %! &! '! (! )! *! "!! ""! "#! "$! "%! "&! "'! "(! ")! "*! #!! +",-../0 #%1$ #&1% %*1$ &)1* '&1$ ')1( (!1& (!1& (!1( ("1) "!)1$ ""'1% ""*1# "#&1' "#&1* "#(1# "$!1' "$%1( "$(1( "&"1* "&&1% "'$1$ C 6 35

36 !"!!"# $"! $"# %"! %"# &"! &"# '"! '"# #"! #"# ("! ("# )"! )"# *"! *"# +"! +"# $!"! $!"#,$-.//01 &"!! &"(( %"+* &"&% %"!# &"*# $"*' $"*+ $")) $"!&!"+% $"$'!"+*!"+)!"+#!"*( %"&) %"($ &"&( &"'% &"#' &"## &"#( &"(# &"(( &"() &"(* &"*& '"'# '"'( '"') )"!( )"%* )"&! )"() )"(* )")) )")+ *"!+ *"%& *"&$ C 14 36

37 ! "! #! $! %! &! '! (! )! *! "!! ""! "#! "$! "%! "&! "'! "(! ")! "*! #!! +",-../0 %'1" %)1! &%1) &*1! '&1% ')1( (!1& (!1' (!1) ("1* **1$ "!)1( ""'1# ""*1! "#'1" "#'1" "#(1% "$!1' "$%1& "$(1& "&"1% "&&1% "'$1# C 14 37

38 C 15 38

39 ! "! #! $! %! &! '! (! )! *! "!! ""! "#! "$! "%! "&! "'! "(! ")! "*! #!! +",-../0 %)1# &)1* '&1% ''1& ')1' (!1% (!1& (!1( ("1) **1% "!)1& ""'1" "")1& "#'1! "#'1" "#(1% "$!1' "$%1% "$(1# "&"1$ "&&1# "'$1! C 15 39

40 !"!!"# $"! $"# %"! %"# &"! &"# '"! '"# #"! #"# ("! ("# )"! )"# *"! *"# +"! +"# $!"! $!"#,$-.//01 &"+* %"$& %"!$ &"!! %"$& '"&* ("%% %"$* %"$!!"++ $"!% $"!) $"!( $"!' $"!' $"!& $"!! %"#$ %"(+ %")! %")$ &"&$ &"&( &"#' &"#( &"(( &"(* &")% &")& '"'# '"'# '"'( '"'( '"') '"+( (")' (")# ("+& ("+' ("+# )"#+ )"($ )"(* )")! *"!) *"!) *"!+ *"!+ *"$+ *"$+ *"%* C 16 H 40

41 ! "! #! $! %! &! '! (! )! *! "!! ""! "#! "$! "%! "&! "'! "(! ")! "*! #!! +",-../0 $*1# &$1# &'1' &*1! '&1$ ''1* ')1) (!1& (!1' (!1) ("1* *)1# "!$1' ""'1& "")1* "#%1* "#'1# "#'1$ "$!1* "$&1! "$)1$ "%*1! "&&1& "'$1% C 16 H 41

42 C 17 42

43 ! "! #! $! %! &! '! (! )! *! "!! ""! "#! "$! "%! "&! "'! "(! ")! "*! #!! +",-../0 #%1# #&1$ %*1# &)1) '&1# ')1' (!1$ (!1% (!1' ("1( *)1% "!)1# ""'1$ ""*1" "#&1& "#&1) "#(1" "$!1& "$%1' "$(1' "&"1) "&&1$ "'$1# C 17 43

44 !"!!"# $"! $"# %"! %"# &"! &"# '"! '"# #"! #"# ("! ("# )"! )"# *"! *"# +"! +"# $!"! $!"#,$-.//01 &"'* &"'* )"#) &"+( $"$) $"%& $"+( $"%( $"%& $"(' $"&# $"$$ $"!( $"!% $"!! $"&+ $"'* $"(( $"() $"(* $")$ $")% &"&* &"'! &"'$ &"** &"+$ '"$% '"&# '"&( '"&) '"'! '"'% '"'& '"'' )"!% )"!& )"%( )"%* )"(% )"(' )")& )")# *"!* *"$! *"$+ *"%+ C 18 44

45 ! "! #! $! %! &! '! (! )! *! "!! ""! "#! "$! "%! "&! "'! "(! ")! "*! #!! +",-../0 #%1! #&1# #'1% #*1% %&1& %*1" &(1" '&1' '&1* ($1" *)1! "!)1# "!*1' ""'1" ""*1! "#&1$ "#&1' "#(1! "$!1& "$%1' "$(1' "&"1& "&&1% "'#1* C 18 45

46 !"!!"# $"! $"# %"! %"# &"! &"# '"! '"# #"! #"# ("! ("# )"! )"# *"! *"# +"! +"# $!"! $!"#,$-.//01 ("!! &"($!"+!!"*&!"*+ $")$ $"!! $"!) $"!'!"+'!"*+!"*%!"*& $"() $"(* $"(+ $")& $")' &"'! &"'$ &"'% &")! &")& &")+ '"!) '"!+ '"$! '"&( '"&* '"&+ '"'! '"'% '"'& '"'' '"'( )"!& )"%( )"%+ )"(% )"(' )")& )")( *"!) *"!+ *"$+ *"&! C 19 H H 46

47 ! "! #! $! %! &! '! (! )! *! "!! ""! "#! "$! "%! "&! "'! "(! ")! "*! #!! +",-../0 #%1$ #&1& #*1( %*1$ '$1# '(1! '*1* *(1) "!)1$ ""'1' ""*1# "#&1& "#&1* "#(1$ "$!1( "$&1! "$(1* "&#1! "&'1! "'$1' C 19 H H 47

Supporting Information

Supporting Information Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2012 Subcellular Localization and Activity of Gambogic Acid Gianni Guizzunti,* [b] Ayse Batova, [a] Oraphin Chantarasriwong,

More information

Supporting Information. Table of Contents. 1. General Notes Experimental Details 3-12

Supporting Information. Table of Contents. 1. General Notes Experimental Details 3-12 Supporting Information Table of Contents page 1. General Notes 2 2. Experimental Details 3-12 3. NMR Support for Timing of Claisen/Diels-Alder/Claisen 13 4. 1 H and 13 C NMR 14-37 General Notes All reagents

More information

Synthetic Studies on Norissolide; Enantioselective Synthesis of the Norrisane Side Chain

Synthetic Studies on Norissolide; Enantioselective Synthesis of the Norrisane Side Chain rganic Lett. (Supporting Information) 1 Synthetic Studies on Norissolide; Enantioselective Synthesis of the Norrisane Side Chain Charles Kim, Richard Hoang and Emmanuel A. Theodorakis* Department of Chemistry

More information

Tetrahydrofuran (THF) was distilled from benzophenone ketyl radical under an argon

Tetrahydrofuran (THF) was distilled from benzophenone ketyl radical under an argon SUPPLEMENTARY METHODS Solvents, reagents and synthetic procedures All reactions were carried out under an argon atmosphere unless otherwise specified. Tetrahydrofuran (THF) was distilled from benzophenone

More information

The First Asymmetric Total Syntheses and. Determination of Absolute Configurations of. Xestodecalactones B and C

The First Asymmetric Total Syntheses and. Determination of Absolute Configurations of. Xestodecalactones B and C Supporting Information The First Asymmetric Total Syntheses and Determination of Absolute Configurations of Xestodecalactones B and C Qiren Liang, Jiyong Zhang, Weiguo Quan, Yongquan Sun, Xuegong She*,,

More information

hydroxyanthraquinones related to proisocrinins

hydroxyanthraquinones related to proisocrinins Supporting Information for Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins Joyeeta Roy, Tanushree Mal, Supriti Jana and Dipakranjan Mal* Address: Department of Chemistry,

More information

Regioselective Synthesis of the Tricyclic Core of Lateriflorone

Regioselective Synthesis of the Tricyclic Core of Lateriflorone Regioselective Synthesis of the Tricyclic Core of Lateriflorone Eric J. Tisdale, Hongmei Li, Binh G. Vong, Sun Hee Kim, Emmanuel A. Theodorakis* Department of Chemistry and Biochemistry, University of

More information

Supporting Material. 2-Oxo-tetrahydro-1,8-naphthyridine-Based Protein Farnesyltransferase Inhibitors as Antimalarials

Supporting Material. 2-Oxo-tetrahydro-1,8-naphthyridine-Based Protein Farnesyltransferase Inhibitors as Antimalarials Supporting Material 2-Oxo-tetrahydro-1,8-naphthyridine-Based Protein Farnesyltransferase Inhibitors as Antimalarials Srinivas Olepu a, Praveen Kumar Suryadevara a, Kasey Rivas b, Christophe L. M. J. Verlinde

More information

Supporting Information for. A New Method for the Cleavage of Nitrobenzyl Amides and Ethers

Supporting Information for. A New Method for the Cleavage of Nitrobenzyl Amides and Ethers SI- 1 Supporting Information for A ew Method for the Cleavage of itrobenzyl Amides and Ethers Seo-Jung Han, Gabriel Fernando de Melo, and Brian M. Stoltz* The Warren and Katharine Schlinger Laboratory

More information

Supporting Information

Supporting Information Meyer, Ferreira, and Stoltz: Diazoacetoacetic acid Supporting Information S1 2-Diazoacetoacetic Acid, an Efficient and Convenient Reagent for the Synthesis of Substituted -Diazo- -ketoesters Michael E.

More information

SYNTHESIS OF A 3-THIOMANNOSIDE

SYNTHESIS OF A 3-THIOMANNOSIDE Supporting Information SYNTHESIS OF A 3-THIOMANNOSIDE María B Comba, Alejandra G Suárez, Ariel M Sarotti, María I Mangione* and Rolando A Spanevello and Enrique D V Giordano Instituto de Química Rosario,

More information

Curtius-Like Rearrangement of Iron-Nitrenoid Complex and. Application in Biomimetic Synthesis of Bisindolylmethanes

Curtius-Like Rearrangement of Iron-Nitrenoid Complex and. Application in Biomimetic Synthesis of Bisindolylmethanes Supporting Information Curtius-Like Rearrangement of Iron-itrenoid Complex and Application in Biomimetic Synthesis of Bisindolylmethanes Dashan Li,, Ting Wu,, Kangjiang Liang,, and Chengfeng Xia*,, State

More information

Stereoselective Synthesis of (-) Acanthoic Acid

Stereoselective Synthesis of (-) Acanthoic Acid 1 Stereoselective Synthesis of (-) Acanthoic Acid Taotao Ling, Bryan A. Kramer, Michael A. Palladino, and Emmanuel A. Theodorakis* Department of Chemistry and Biochemistry, University of California, San

More information

Synthesis of Trifluoromethylated Naphthoquinones via Copper-Catalyzed. Cascade Trifluoromethylation/Cyclization of. 2-(3-Arylpropioloyl)benzaldehydes

Synthesis of Trifluoromethylated Naphthoquinones via Copper-Catalyzed. Cascade Trifluoromethylation/Cyclization of. 2-(3-Arylpropioloyl)benzaldehydes Supporting Information to Synthesis of Trifluoromethylated Naphthoquinones via Copper-Catalyzed Cascade Trifluoromethylation/Cyclization of 2-(3-Arylpropioloyl)benzaldehydes Yan Zhang*, Dongmei Guo, Shangyi

More information

Supplementary Table S1: Response evaluation of FDA- approved drugs

Supplementary Table S1: Response evaluation of FDA- approved drugs SUPPLEMENTARY DATA, FIGURES AND TABLE BIOLOGICAL DATA Spheroids MARY-X size distribution, morphology and drug screening data Supplementary Figure S1: Spheroids MARY-X size distribution. Spheroid size was

More information

A Strategy Toward the Synthesis of C 13 -Oxidized Cembrenolides

A Strategy Toward the Synthesis of C 13 -Oxidized Cembrenolides A Strategy Toward the Synthesis of C 13 -xidized Cembrenolides Alec Saitman, Steven D. E. Sullivan and Emmanuel A. Theodorakis* Department of Chemistry and Biochemistry, University of California, San Diego,

More information

Supporting Information

Supporting Information An Improved ynthesis of the Pyridine-Thiazole Cores of Thiopeptide Antibiotics Virender. Aulakh, Marco A. Ciufolini* Department of Chemistry, University of British Columbia 2036 Main Mall, Vancouver, BC

More information

Supporting Information for: Tuning the Binding Properties of a New Heteroditopic Salt Receptor Through Embedding in a Polymeric System

Supporting Information for: Tuning the Binding Properties of a New Heteroditopic Salt Receptor Through Embedding in a Polymeric System Supporting Information for: Tuning the Binding Properties of a ew Heteroditopic Salt Receptor Through Embedding in a Polymeric System Jan Romanski* and Piotr Piątek* Department of Chemistry, University

More information

Supporting Information

Supporting Information Supporting Information Divergent Reactivity of gem-difluoro-enolates towards Nitrogen Electrophiles: Unorthodox Nitroso Aldol Reaction for Rapid Synthesis of -Ketoamides Mallu Kesava Reddy, Isai Ramakrishna,

More information

Supporting Information For:

Supporting Information For: Supporting Information For: Peptidic α-ketocarboxylic Acids and Sulfonamides as Inhibitors of Protein Tyrosine Phosphatases Yen Ting Chen, Jian Xie, and Christopher T. Seto* Department of Chemistry, Brown

More information

Supporting Information

Supporting Information Supporting Information Total Synthesis of (±)-Grandilodine B Chunyu Wang, Zhonglei Wang, Xiaoni Xie, Xiaotong Yao, Guang Li, and Liansuo Zu* School of Pharmaceutical Sciences, Tsinghua University, Beijing,

More information

Supporting Information

Supporting Information Supporting Information (Tetrahedron. Lett.) Cavitands with Inwardly and Outwardly Directed Functional Groups Mao Kanaura a, Kouhei Ito a, Michael P. Schramm b, Dariush Ajami c, and Tetsuo Iwasawa a * a

More information

Indium Triflate-Assisted Nucleophilic Aromatic Substitution Reactions of. Nitrosobezene-Derived Cycloadducts with Alcohols

Indium Triflate-Assisted Nucleophilic Aromatic Substitution Reactions of. Nitrosobezene-Derived Cycloadducts with Alcohols Supporting Information Indium Triflate-Assisted ucleophilic Aromatic Substitution Reactions of itrosobezene-derived Cycloadducts with Alcohols Baiyuan Yang and Marvin J. Miller* Department of Chemistry

More information

Electronic Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is The Royal Society of Chemistry 2012

Electronic Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is The Royal Society of Chemistry 2012 Supporting Information. Experimental Section: Summary scheme H 8 H H H 9 a H C 3 1 C 3 A H H b c C 3 2 3 C 3 H H d e C 3 4 5 C 3 H f g C 2 6 7 C 2 H a C 3 B H c C 3 General experimental details: All solvents

More information

Efficient Mono- and Bis-Functionalization of 3,6-Dichloropyridazine using (tmp) 2 Zn 2MgCl 2 2LiCl ** Stefan H. Wunderlich and Paul Knochel*

Efficient Mono- and Bis-Functionalization of 3,6-Dichloropyridazine using (tmp) 2 Zn 2MgCl 2 2LiCl ** Stefan H. Wunderlich and Paul Knochel* Efficient Mono- and Bis-Functionalization of 3,6-Dichloropyridazine using (tmp) 2 Zn 2Mg 2 2Li ** Stefan H. Wunderlich and Paul Knochel* Ludwig Maximilians-Universität München, Department Chemie & Biochemie

More information

Phil S. Baran*, Jeremy M. Richter and David W. Lin SUPPORTING INFORMATION

Phil S. Baran*, Jeremy M. Richter and David W. Lin SUPPORTING INFORMATION Direct Coupling of Pyrroles with Carbonyl Compounds: Short, Enantioselective Synthesis of (S)-Ketorolac Phil S. Baran*, Jeremy M. Richter and David W. Lin SUPPRTIG IFRMATI General Procedures. All reactions

More information

Synthesis of Glaucogenin D, a Structurally Unique. Disecopregnane Steroid with Potential Antiviral Activity

Synthesis of Glaucogenin D, a Structurally Unique. Disecopregnane Steroid with Potential Antiviral Activity Supporting Information for Synthesis of Glaucogenin D, a Structurally Unique Disecopregnane Steroid with Potential Antiviral Activity Jinghan Gui,* Hailong Tian, and Weisheng Tian* Key Laboratory of Synthetic

More information

Supplementary Material

Supplementary Material 10.1071/CH13324_AC CSIRO 2013 Australian Journal of Chemistry 2013, 66(12), 1570-1575 Supplementary Material A Mild and Convenient Synthesis of 1,2,3-Triiodoarenes via Consecutive Iodination/Diazotization/Iodination

More information

Supporting Information:

Supporting Information: Enantioselective Synthesis of (-)-Codeine and (-)-Morphine Barry M. Trost* and Weiping Tang Department of Chemistry, Stanford University, Stanford, CA 94305-5080 1. Aldehyde 7. Supporting Information:

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION Supplementary Method Synthesis of 2-alkyl-MPT(R) General information (R) enantiomer of 2-alkyl (18:1) MPT (hereafter designated as 2-alkyl- MPT(R)), was synthesized as previously described 1, with some

More information

Supporting Information for Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers: Approaches to Diazonamide A

Supporting Information for Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers: Approaches to Diazonamide A Fuerst et al. Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers: Approaches to Diazonamide A S1 Supporting Information for Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers:

More information

SUPPORTING INFORMATION

SUPPORTING INFORMATION Dynamic covalent templated-synthesis of [c2]daisy chains. Altan Bozdemir, a Gokhan Barin, a Matthew E. Belowich, a Ashish. Basuray, a Florian Beuerle, a and J. Fraser Stoddart* ab a b Department of Chemistry,

More information

Supporting Text Synthesis of (2 S ,3 S )-2,3-bis(3-bromophenoxy)butane (3). Synthesis of (2 S ,3 S

Supporting Text Synthesis of (2 S ,3 S )-2,3-bis(3-bromophenoxy)butane (3). Synthesis of (2 S ,3 S Supporting Text Synthesis of (2S,3S)-2,3-bis(3-bromophenoxy)butane (3). Under N 2 atmosphere and at room temperature, a mixture of 3-bromophenol (0.746 g, 4.3 mmol) and Cs 2 C 3 (2.81 g, 8.6 mmol) in DMS

More information

Supporting Information

Supporting Information Supporting Information Construction of Highly Functional α-amino itriles via a ovel Multicomponent Tandem rganocatalytic Reaction: a Facile Access to α-methylene γ-lactams Feng Pan, Jian-Ming Chen, Zhe

More information

An Efficient Total Synthesis and Absolute Configuration. Determination of Varitriol

An Efficient Total Synthesis and Absolute Configuration. Determination of Varitriol An Efficient Total Synthesis and Absolute Configuration Determination of Varitriol Ryan T. Clemens and Michael P. Jennings * Department of Chemistry, University of Alabama, 500 Campus Dr. Tuscaloosa, AL

More information

How to build and race a fast nanocar Synthesis Information

How to build and race a fast nanocar Synthesis Information How to build and race a fast nanocar Synthesis Information Grant Simpson, Victor Garcia-Lopez, Phillip Petemeier, Leonhard Grill*, and James M. Tour*, Department of Physical Chemistry, University of Graz,

More information

Experimental details

Experimental details Supporting Information for A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyx) ligand Hideki Shimizu 1,2, Jeffrey C. Holder 1 and Brian M. Stoltz* 1 Address:

More information

Formal Total Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis

Formal Total Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis Formal Total Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis Kazushi Watanabe, Yuto Suzuki, Kenta Aoki, Akira Sakakura, Kiyotake Suenaga, and Hideo Kigoshi* Department of Chemistry,

More information

Synthesis and Use of QCy7-derived Modular Probes for Detection and. Imaging of Biologically Relevant Analytes. Supplementary Methods

Synthesis and Use of QCy7-derived Modular Probes for Detection and. Imaging of Biologically Relevant Analytes. Supplementary Methods Synthesis and Use of QCy7-derived Modular Probes for Detection and Imaging of Biologically Relevant Analytes Supplementary Methods Orit Redy a, Einat Kisin-Finfer a, Shiran Ferber b Ronit Satchi-Fainaro

More information

Synthesis of fluorophosphonylated acyclic nucleotide analogues via Copper (I)- catalyzed Huisgen 1-3 dipolar cycloaddition

Synthesis of fluorophosphonylated acyclic nucleotide analogues via Copper (I)- catalyzed Huisgen 1-3 dipolar cycloaddition Synthesis of fluorophosphonylated acyclic nucleotide analogues via Copper (I)- catalyzed Huisgen 1-3 dipolar cycloaddition Sonia Amel Diab, Antje Hienzch, Cyril Lebargy, Stéphante Guillarme, Emmanuel fund

More information

A Mild, Catalytic and Highly Selective Method for the Oxidation of α,β- Enones to 1,4-Enediones. Jin-Quan Yu, a and E. J.

A Mild, Catalytic and Highly Selective Method for the Oxidation of α,β- Enones to 1,4-Enediones. Jin-Quan Yu, a and E. J. A Mild, Catalytic and Highly Selective Method for the Oxidation of α,β- Enones to 1,4-Enediones Jin-Quan Yu, a and E. J. Corey b * a Department of Chemistry, Cambridge University, Cambridge CB2 1EW, United

More information

Copper-Catalyzed Oxidative Cyclization of Carboxylic Acids

Copper-Catalyzed Oxidative Cyclization of Carboxylic Acids Copper-Catalyzed xidative Cyclization of Carboxylic Acids Supplementary material (51 pages) Shyam Sathyamoorthi and J. Du Bois * Department of Chemistry Stanford University Stanford, CA 94305-5080 General.

More information

Electronic Supplementary Information. An Ultrafast Surface-Bound Photo-active Molecular. Motor

Electronic Supplementary Information. An Ultrafast Surface-Bound Photo-active Molecular. Motor This journal is The Royal Society of Chemistry and wner Societies 2013 Electronic Supplementary Information An Ultrafast Surface-Bound Photo-active Molecular Motor Jérôme Vachon, [a] Gregory T. Carroll,

More information

Supplementary Note 1 : Chemical synthesis of (E/Z)-4,8-dimethylnona-2,7-dien-4-ol (4)

Supplementary Note 1 : Chemical synthesis of (E/Z)-4,8-dimethylnona-2,7-dien-4-ol (4) Supplementary Note 1 : Chemical synthesis of (E/Z)-4,8-dimethylnona-2,7-dien-4-ol (4) A solution of propenyl magnesium bromide in THF (17.5 mmol) under nitrogen atmosphere was cooled in an ice bath and

More information

Electronic Supplementary Information for. A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective

Electronic Supplementary Information for. A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective Electronic Supplementary Information for A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective and Sensitive Detection of H 2 S: Synthesis, Spectra and Bioimaging Changyu Zhang, 1 Runyu Wang,

More information

Supporting Information. (1S,8aS)-octahydroindolizidin-1-ol.

Supporting Information. (1S,8aS)-octahydroindolizidin-1-ol. SI-1 Supporting Information Non-Racemic Bicyclic Lactam Lactones Via Regio- and cis-diastereocontrolled C H insertion. Asymmetric Synthesis of (8S,8aS)-octahydroindolizidin-8-ol and (1S,8aS)-octahydroindolizidin-1-ol.

More information

Supporting Information

Supporting Information Supporting Information Precision Synthesis of Poly(-hexylpyrrole) and its Diblock Copolymer with Poly(p-phenylene) via Catalyst-Transfer Polycondensation Akihiro Yokoyama, Akira Kato, Ryo Miyakoshi, and

More information

An unusual dianion equivalent from acylsilanes for the synthesis of substituted β-keto esters

An unusual dianion equivalent from acylsilanes for the synthesis of substituted β-keto esters S1 An unusual dianion equivalent from acylsilanes for the synthesis of substituted β-keto esters Chris V. Galliford and Karl A. Scheidt* Department of Chemistry, Northwestern University, 2145 Sheridan

More information

Supporting Information for

Supporting Information for Electronic Supplementary Material (ESI) for New Journal of Chemistry. This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2017 Supporting Information for

More information

N-Hydroxyphthalimide: a new photoredox catalyst for [4+1] radical cyclization of N-methylanilines with isocyanides

N-Hydroxyphthalimide: a new photoredox catalyst for [4+1] radical cyclization of N-methylanilines with isocyanides Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2016 Electronic supplementary information for -Hydroxyphthalimide: a new photoredox catalyst for [4+1]

More information

Electronic Supplementary Material (ESI) for Chemical Communications This journal is The Royal Society of Chemistry 2012

Electronic Supplementary Material (ESI) for Chemical Communications This journal is The Royal Society of Chemistry 2012 Ring Expansion of Alkynyl Cyclopropanes to Highly substituted Cyclobutenes via a N-Sulfonyl-1,2,3-Triazole Intermediate Renhe Liu, Min Zhang, Gabrielle Winston-Mcerson, and Weiping Tang* School of armacy,

More information

Discovery of 3-substituted 1H-indole-2-carboxylic Acid Derivatives as a Novel Class of CysLT 1 Selective Antagonists

Discovery of 3-substituted 1H-indole-2-carboxylic Acid Derivatives as a Novel Class of CysLT 1 Selective Antagonists Discovery of 3-substituted 1H-indole-2-carboxylic Acid Derivatives as a Novel Class of CysLT 1 Selective Antagonists Huayan Chen,,b Hui Yang, #, b Zhilong Wang, # Xin Xie, #, * Fajun Nan, * State Key Laboratory

More information

Supporting Information

Supporting Information Supporting Information Organocatalytic Enantioselective Formal Synthesis of Bromopyrrole Alkaloids via Aza-Michael Addition Su-Jeong Lee, Seok-Ho Youn and Chang-Woo Cho* Department of Chemistry, Kyungpook

More information

Supporting Information for

Supporting Information for Page of 0 0 0 0 Submitted to The Journal of Organic Chemistry S Supporting Information for Syntheses and Spectral Properties of Functionalized, Water-soluble BODIPY Derivatives Lingling Li, Junyan Han,

More information

Phil S. Baran*, Ryan A. Shenvi, Christos Mitsos SUPPORTING INFORMATION

Phil S. Baran*, Ryan A. Shenvi, Christos Mitsos SUPPORTING INFORMATION A Remarkable Ring Contraction En Route to the Chartelline Alkaloids Phil S. Baran*, Ryan A. Shenvi, Christos Mitsos Contribution from the Department of Chemistry, The Scripps Research Institute, 10550

More information

Scalable Synthesis of Fmoc-Protected GalNAc-Threonine Amino Acid and T N Antigen via Nickel Catalysis

Scalable Synthesis of Fmoc-Protected GalNAc-Threonine Amino Acid and T N Antigen via Nickel Catalysis Scalable Synthesis of Fmoc-Protected GalNAc-Threonine Amino Acid and T N Antigen via Nickel Catalysis Fei Yu, Matthew S. McConnell, and Hien M. Nguyen* Department of Chemistry, University of Iowa, Iowa

More information

Diastereoselectivity in the Staudinger reaction of. pentafluorosulfanylaldimines and ketimines

Diastereoselectivity in the Staudinger reaction of. pentafluorosulfanylaldimines and ketimines Supporting Information for Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines Alexander Penger, Cortney. von ahmann, Alexander S. Filatov and John T. Welch* Address:

More information

Supporting Information

Supporting Information Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 214 Supporting Information Rapid and sensitive detection of acrylic acid using a novel fluorescence

More information

SUPPORTING INFORMATION

SUPPORTING INFORMATION SUPPRTING INFRMATIN A Direct, ne-step Synthesis of Condensed Heterocycles: A Palladium-Catalyzed Coupling Approach Farnaz Jafarpour and Mark Lautens* Davenport Chemical Research Laboratories, Chemistry

More information

Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801.

Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801. Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801. Alan L. Sewell a, Mathew V. J. Villa a, Mhairi Matheson a, William G. Whittingham b, Rodolfo Marquez a*. a) WestCHEM, School of Chemistry,

More information

Ring-Opening / Fragmentation of Dihydropyrones for the Synthesis of Homopropargyl Alcohols

Ring-Opening / Fragmentation of Dihydropyrones for the Synthesis of Homopropargyl Alcohols Ring-pening / Fragmentation of Dihydropyrones for the Synthesis of Homopropargyl Alcohols Jumreang Tummatorn, and Gregory B. Dudley, * Department of Chemistry and Biochemistry, Florida State University,

More information

Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA Experimental Procedures

Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA Experimental Procedures Supporting Information Low Temperature n-butyllithium-induced [3,3]-Sigmatropic Rearrangement/Electrophile Trapping Reactions of Allyl-1,1- Dichlorovinyl Ethers. Synthesis of - - and -lactones. Aaron Christopher

More information

Electronic Supplementary Information

Electronic Supplementary Information Electronic Supplementary Material (ESI) for rganic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2014 Electronic Supplementary Information Visible light-mediated dehydrogenative

More information

Supporting Information

Supporting Information Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 2016 Supporting Information TEMPO-catalyzed Synthesis of 5-Substituted Isoxazoles from Propargylic

More information

Reactions. James C. Anderson,* Rachel H. Munday. School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK

Reactions. James C. Anderson,* Rachel H. Munday. School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK Vinyl-dimethylphenylsilanes as Safety Catch Silanols in Fluoride free Palladium Catalysed Cross Coupling Reactions. James C. Anderson,* Rachel H. Munday School of Chemistry, University of Nottingham, Nottingham,

More information

A Closer Look at the Bromine-Lithium Exchange with

A Closer Look at the Bromine-Lithium Exchange with SUPPRTIG IFRMATI A Closer Look at the Bromine-Lithium Exchange with tert-butyllithium in an Aryl Sulfonamide Synthesis Christopher Waldmann,*, tmar Schober, Günter Haufe, and Klaus Kopka, Department of

More information

Synthesis of Levulinic Acid based Poly(amine-co-ester)s

Synthesis of Levulinic Acid based Poly(amine-co-ester)s Electronic Supplementary Material (ESI) for Green Chemistry. This journal is The Royal Society of Chemistry 2018 Synthesis of Levulinic Acid based Poly(amine-co-ester)s Yann Bernhard, Lucas Pagies, Sylvain

More information

Light-Controlled Switching of a Non- Photoresponsive Molecular Shuttle

Light-Controlled Switching of a Non- Photoresponsive Molecular Shuttle Supporting Information Light-Controlled Switching of a Non- Photoresponsive Molecular Shuttle Liu-Pan Yang, a,b Fei Jia, a Jie-Shun Cui, a Song-Bo Lu, a and Wei Jiang* a a Department of Chemistry, South

More information

Supporting Information

Supporting Information Supporting Information Lewis acid-catalyzed intramolecular condensation of ynol ether-acetals. Synthesis of alkoxycycloalkene carboxylates Vincent Tran and Thomas G. Minehan * Department of Chemistry and

More information

Photooxidations of 2-(γ,ε-dihydroxyalkyl) furans in Water: Synthesis of DE-Bicycles of the Pectenotoxins

Photooxidations of 2-(γ,ε-dihydroxyalkyl) furans in Water: Synthesis of DE-Bicycles of the Pectenotoxins S1 Photooxidations of 2-(γ,ε-dihydroxyalkyl) furans in Water: Synthesis of DE-Bicycles of the Pectenotoxins Antonia Kouridaki, Tamsyn Montagnon, Maria Tofi and Georgios Vassilikogiannakis* Department of

More information

Rational design of a ratiometric fluorescent probe with a large emission shift for the facile detection of Hg 2+

Rational design of a ratiometric fluorescent probe with a large emission shift for the facile detection of Hg 2+ Rational design of a ratiometric fluorescent probe with a large emission shift for the facile detection of Hg 2+ Weimin Xuan, a Chen Chen, b Yanting Cao, a Wenhan He, a Wei Jiang, a Kejian Li, b* and Wei

More information

A Photocleavable Linker for the Chemoselective Functionalization of Biomaterials

A Photocleavable Linker for the Chemoselective Functionalization of Biomaterials Electronic Supplementary Information A otocleavable Linker for the Chemoselective Functionalization of Biomaterials Liz Donovan and Paul A. De Bank* Department of armacy and armacology and Centre for Regenerative

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2011 69451 Weinheim, Germany Enantioselective Total Synthesis of ( )-Jiadifenolide** Jing Xu, Lynnie Trzoss, Weng K. Chang, and Emmanuel A. Theodorakis* anie_201100313_sm_miscellaneous_information.pdf

More information

1G (bottom) with the phase-transition temperatures in C and associated enthalpy changes (in

1G (bottom) with the phase-transition temperatures in C and associated enthalpy changes (in Supplementary Figure 1. Optical properties of 1 in various solvents. UV/Vis (left axis) and fluorescence spectra (right axis, ex = 420 nm) of 1 in hexane (blue lines), toluene (green lines), THF (yellow

More information

Supporting Information

Supporting Information Supporting Information An Extremely Active and General Catalyst for Suzuki Coupling Reactions of Unreactive Aryl Chlorides Dong-Hwan Lee and Myung-Jong Jin* School of Chemical Science and Engineering,

More information

Supporting Information

Supporting Information Supporting Information for Cu-Mediated trifluoromethylation of benzyl, allyl and propargyl methanesulfonates with TMSCF 3 Xueliang Jiang 1 and Feng-Ling Qing* 1,2 Address: 1 Key Laboratory of Organofluorine

More information

Synthesis of 2- and 4-hydroxymethyl Loratadine, usual impurities in Loratadine syrup formulations

Synthesis of 2- and 4-hydroxymethyl Loratadine, usual impurities in Loratadine syrup formulations Issue in Honor of Prof. J. Elguero and P. Molina ARKIVC 2005 (ix) 200-206 Synthesis of 2- and 4-hydroxymethyl Loratadine, usual impurities in Loratadine syrup formulations Verónica Cerrada, M. Paz Matía-Martín,

More information

Supporting Information

Supporting Information Supporting Information Towards Singlet Oxygen Delivery at a Measured Rate: A Selfreporting Photosensitizer Sundus Erbas-Cakmak #, Engin U. Akkaya # * # UNAM-National Nanotechnology Research Center, Bilkent

More information

Enantioselective Conjugate Addition of 3-Fluoro-Oxindoles to. Vinyl Sulfone: An Organocatalytic Access to Chiral. 3-Fluoro-3-Substituted Oxindoles

Enantioselective Conjugate Addition of 3-Fluoro-Oxindoles to. Vinyl Sulfone: An Organocatalytic Access to Chiral. 3-Fluoro-3-Substituted Oxindoles Enantioselective Conjugate Addition of 3-Fluoro-Oxindoles to Vinyl Sulfone: An Organocatalytic Access to Chiral 3-Fluoro-3-Substituted Oxindoles Xiaowei Dou and Yixin Lu * Department of Chemistry & Medicinal

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2006 69451 Weinheim, Germany rganocatalytic Conjugate Addition of Malonates to a,ß-unsaturated Aldehydes: Asymmetric Formal Synthesis of (-)-Paroxetine, Chiral Lactams

More information

J. Am. Chem. Soc. Supporting Information Page 1

J. Am. Chem. Soc. Supporting Information Page 1 J. Am. Chem. Soc. Supporting Information Page 1 Short Total Synthesis of (±)-Sceptrin Phil S. Baran*, Alexandros L. Zografos, and Daniel P. Malley Contribution from the Department of Chemistry, The Scripps

More information

Synthesis of borinic acids and borinate adducts using diisopropylaminoborane

Synthesis of borinic acids and borinate adducts using diisopropylaminoborane Synthesis of borinic acids and borinate adducts using diisopropylaminoborane Ludovic Marciasini, Bastien Cacciuttolo, Michel Vaultier and Mathieu Pucheault* Institut des Sciences Moléculaires, UMR 5255,

More information

Modular, Scalable Synthesis of Group A Streptogramin Antibiotics

Modular, Scalable Synthesis of Group A Streptogramin Antibiotics Supporting Information for Modular, Scalable Synthesis of Group A Streptogramin Antibiotics Qi Li and Ian B. Seiple* Department of Pharmaceutical Chemistry and Cardiovascular Research Institute, University

More information

SUPPORTING INFORMATION

SUPPORTING INFORMATION UPPRTING INFRMATIN Application of a Rhodium-Catalyzed Addition/Cyclization equence Toward the ynthesis of Polycyclic eteroaromatics Nai-Wen Tseng and Mark Lautens* Davenport Laboratories, Chemistry Department,

More information

A Highly Efficient Synthesis of Telaprevir by Strategic Use of Biocatalysis and Multicomponent Reactions

A Highly Efficient Synthesis of Telaprevir by Strategic Use of Biocatalysis and Multicomponent Reactions Supporting Information A ighly Efficient Synthesis of Telaprevir by Strategic Use of Biocatalysis and Multicomponent Reactions Anass Znabet, Marloes M. Polak, Elwin Janssen, Frans J. J. de Kanter, icholas

More information

Directed Heterodimerization: Stereocontrolled Fragment Assembly via Solvent-Caged Unsymmetrical Diazene Fragmentation. Supporting Information

Directed Heterodimerization: Stereocontrolled Fragment Assembly via Solvent-Caged Unsymmetrical Diazene Fragmentation. Supporting Information Page S1/S74 Directed Heterodimerization: Stereocontrolled Fragment Assembly via Solvent-Caged Unsymmetrical Diazene Fragmentation Massachusetts Institute of Technology, Department of Chemistry, Massachusetts

More information

A "turn-on" coumarin-based fluorescent sensor with high selectivity for mercury ions in aqueous media

A turn-on coumarin-based fluorescent sensor with high selectivity for mercury ions in aqueous media A "turn-on" coumarin-based fluorescent sensor with high selectivity for mercury ions in aqueous media Styliani Voutsadaki, George K. Tsikalas, Emmanuel Klontzas, George E. Froudakis, and Haralambos E.

More information

Supporting Information for: Phosphonates

Supporting Information for: Phosphonates Supporting Information for: A Room-Temperature Alternative to the Arbuzov Reaction: the Reductive Deoxygenation of Acyl Phosphonates Sean M. A. Kedrowski and Dennis A. Dougherty* Division of Chemistry

More information

Block: Synthesis, Aggregation-Induced Emission, Two-Photon. Absorption, Light Refraction, and Explosive Detection

Block: Synthesis, Aggregation-Induced Emission, Two-Photon. Absorption, Light Refraction, and Explosive Detection Electronic Supplementary Information (ESI) Luminogenic Materials Constructed from Tetraphenylethene Building Block: Synthesis, Aggregation-Induced Emission, Two-Photon Absorption, Light Refraction, and

More information

Supporting Information

Supporting Information Supporting Information SmI 2 -Mediated Carbon-Carbon Bond Fragmentation in α-aminomethyl Malonates Qiongfeng Xu,, Bin Cheng, $, Xinshan Ye,*, and Hongbin Zhai*,,,$ The State Key Laboratory of Natural and

More information

Supplementary Materials

Supplementary Materials Supplementary Materials ORTHOGOALLY POSITIOED DIAMIO PYRROLE- AD IMIDAZOLE- COTAIIG POLYAMIDES: SYTHESIS OF 1-(3-SUBSTITUTED-PROPYL)-4- ITROPYRROLE-2-CARBOXYLIC ACID AD 1-(3-CHLOROPROPYL)-4- ITROIMIDAZOLE-2-CARBOXYLIC

More information

Supporting Information

Supporting Information Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2014 Supporting Information Pd-Catalyzed C-H Activation/xidative Cyclization of Acetanilide with orbornene:

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2006 69451 Weinheim, Germany A Highly Enantioselective Brønsted Acid Catalyst for the Strecker Reaction Magnus Rueping, * Erli Sugiono and Cengiz Azap General: Unless otherwise

More information

Biobased solvents for the Baylis-Hillman reaction of HMF

Biobased solvents for the Baylis-Hillman reaction of HMF Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 15 Biobased solvents for the Baylis-Hillman reaction of HMF Jia-Neng Tan, a b Mohammed Ahmar a and

More information

Supporting Information. Rh (III)-Catalyzed Meta-C H Olefination Directed by a Nitrile Template

Supporting Information. Rh (III)-Catalyzed Meta-C H Olefination Directed by a Nitrile Template Supporting Information Rh (III)-Catalyzed Meta-C H Olefination Directed by a Nitrile Template Hua-Jin Xu, Yi Lu, *, Marcus E. Farmer, Huai-Wei Wang, Dan Zhao, Yan-Shang Kang, Wei-Yin Sun, *, Jin-Quan Yu

More information

Supporting information

Supporting information Supporting information The L-rhamnose Antigen: a Promising Alternative to α-gal for Cancer Immunotherapies Wenlan Chen,, Li Gu,#, Wenpeng Zhang, Edwin Motari, Li Cai, Thomas J. Styslinger, and Peng George

More information

Supplementary Material for: Unexpected Decarbonylation during an Acid- Mediated Cyclization to Access the Carbocyclic Core of Zoanthenol.

Supplementary Material for: Unexpected Decarbonylation during an Acid- Mediated Cyclization to Access the Carbocyclic Core of Zoanthenol. Tetrahedron Letters 1 Pergamon TETRAHEDRN LETTERS Supplementary Material for: Unexpected Decarbonylation during an Acid- Mediated Cyclization to Access the Carbocyclic Core of Zoanthenol. Jennifer L. Stockdill,

More information

Supporting Information

Supporting Information Supporting Information An efficient and general method for the Heck and Buchwald- Hartwig coupling reactions of aryl chlorides Dong-Hwan Lee, Abu Taher, Shahin Hossain and Myung-Jong Jin* Department of

More information

Compound Number. Synthetic Procedure

Compound Number. Synthetic Procedure Compound Number 1 2 3 4 5 Synthetic Procedure Compound 1, KY1220, (Z)-5-((1-(4-nitrophenyl)-1H-pyrrol-2-yl)methylene)-2-thioxoimidazolidin-4-one was purchased from Chemdiv, Catalog #3229-2677, 97% HPLC

More information

Electronic Supplementary Information. Highly Efficient Deep-Blue Emitting Organic Light Emitting Diode Based on the

Electronic Supplementary Information. Highly Efficient Deep-Blue Emitting Organic Light Emitting Diode Based on the Electronic Supplementary Information Highly Efficient Deep-Blue Emitting rganic Light Emitting Diode Based on the Multifunctional Fluorescent Molecule Comprising Covalently Bonded Carbazole and Anthracene

More information